BME Seminar Series - Hanyang Huang, Audrey Nguyen, & Arghavan Farzadi
"Modulation of biomimetic mineralization of collagen by soluble ectodomain of discoidin domain receptor 2"
Collagen fibrils serve as the major template for mineral deposits in both natural and engineered tissues. In recent years certain non-collagenous proteins have been elucidated as important players in differentially modulating intra vs. extra-fibrillar mineralization of collagen. We and others have previously shown that the expression of the collagen receptor, discoidin domain receptor 2 (DDR2) positively correlates with matrix mineralization. The objective of this study was to examine if the ectodomain (ECD) of DDR2 modulates intra versus extrafibrillar mineralization of collagen independent of cell-signaling. For this purpose, a commonly used biomaterial, namely glutaraldehyde fixed porcine pericardium (GFPP) was subjected to biomimetic mineralization protocols. GFPP was incubated in modified simulated body fluid (mSBF) or polymer-induced liquid precursor (PILP) solutions in the presence of recombinant DDR2 ECD (DDR2-Fc) to mediate extra or intra-fibrillar mineralization of collagen. Thermogravimetric analysis revealed that DDR2-Fc increased mineral content and the matrix to mineral ratio in GFPP calcified in mSBF while no significant differences were observed in PILP mediated mineralization. Electron microscopy approaches were used to evaluate the quality and quantity mineral deposits. An increase in the frequency of particles and size of mineral deposits, was observed in the presence of DDR2-Fc in mSBF. Von Kossa staining and immunohistochemistry analysis of adjacent sections indicated that DDR2-Fc bound to both the matrix and mineral phase of GFPP. Further, DDR2-Fc was found to bind to hydroxyapatite (HAP) particles and enhance the nucleation of mineral deposits in mSBF solutions independent of collagen. Taken together, our observations elucidate DDR2 ECD as a novel player in the modulation of extra-fibrillar mineralization of collagen.
"Adaptive optofluidic imaging using low-aberration elastomer-liquid lenses"
Advanced imaging capabilities, such as wide-angle imaging, stereoscopic vision, and depth perception, are often preferable in optical imaging systems. In conventional optical imaging systems, these functions are typically achieved through replacement and/or displacement of multiple solid optical elements. This may complicate the optical system configuration and increase the overall device dimension and cost. New adaptive optics approaches that can incorporate advanced imaging capabilities in miniature imaging systems are thus of imperative needs. Optofluidic elastomer-liquid lenses have attracted considerable attention in the recent past. They provide a new route for designing and improving miniature and adaptive imaging devices by courtesy of their compact size and tunable optical powers. However, the low image resolution due to optical aberrations remains as a primary limitation of optofluidic lenses. There are few studies providing a practical approach to compensating optical aberrations without compromising the miniaturization and the range of adaptive refractive power. In this study, different strategies for reducing optical aberration of elastomer liquid lenses were investigated, including changing the shape of the lens membrane, i.e. using an inhomogeneous lens membrane and changing the lens configurations, i.e. using a meniscus lens configuration or a biconvex configuration. Results showed that all approaches were effective in reducing optical aberrations. Based on these results, various advanced imaging capabilities using low-aberration elastomer-liquid lenses were demonstrated, including smartphone-based scanning microscopy, switchable 2D/3D imaging, wide-angle imaging with depth perception, whole slide imaging, ‘after-the-fact’ focusing, etc. This study provides a powerful solution to overcome the bottleneck of optical aberration limitations for elastomer-liquid lenses and is expected to foster new imaging capabilities in a miniature and low-cost way.
"Biomechanical Impact of the Sclera on Corneal Deformation Response to an Air-Puff"
Glaucoma is the leading cause of irreversible blindness worldwide and results from the death of retinal ganglion cells. Altered mechanical properties of the sclera have been implicated in the pathogenesis of glaucoma. To our knowledge, a method for the clinical evaluation of scleral properties has yet to be devised. We have sought to address this deficiency using a commercially-available non-contact tonometer and an inverse finite-element analysis.
It has been shown that changing the boundary conditions of the cornea will affect the biomechanical deformation response of the cornea during air-puff induced deformation. A finite-element model was developed to show how varying scleral properties will alter the corneal biomechanical response to an air-puff. The results of the model were validated against results from ex vivo experiments using human donor eyes.
The impact of the sclera on corneal deformation response may have important clinical implications. In clinical settings, the observed corneal biomechanical deformation response is attributed solely to the properties of the cornea. The results of this work suggest that the observed biomechanical response to an air-puff may be used to deduce intraocular pressure and mechanical properties of ocular tissues, potentially leading to improved diagnostic capabilities for glaucoma.